PROJECT SUMMARY Lower back and neck pain is a profoundly debilitating and prevalent condition. It is currently the worldwide leading cause of disability and is a major cause of lost work-days in Western society. The economic burden of this condition is conservatively estimated at $100-200 billion each year. Low back pain and intervertebral disc (IVD) health are inexorably linked. While the cellular events leading to painful degenerate IVDs are well characterized, the initiating events as well as the molecular relationship between disc degeneration and pain are not understood. Recent clinical studies implicate subclinical bacterial infection in the genesis of LBP; not only were multiple strains of Proprionibacterium acnes (P. acnes) isolated from painful herniated IVDs, but long term antibiotic treatment lead to a significant reduction of both disease-specific disability and back pain intensity. Despite the drawback of long-term antibiotic use, the striking success of treating LBP with antibiotics cannot be overlooked. Currently, there is no active research examining the molecular relationship between P. acnes and the pathogenesis of disc disease. From this perspective, understanding how P. acnes influences inflammation and immune cell function is likely to provide a new approach to understanding the relationship between the degenerative response and pain, thus creating a dramatic and transformative shift in treatment options for patients suffering from this pervasive, and often crippling condition.